Ultraviolet irradiation causes skin photoaging and cancer (Yaar & Gilchrest, Br J Dermatol 157:874-887, 2007; Kulms & Schwarz, J Investig Dermatol Symp Proc 7:46-50, 2002; Matsumura & Ananthaswamy, Toxicol Appl Pharmacol 195:298-308, 2004; Gilchrest et al., N Engl J Med 340:1341-1348, 1999; Miller et al., Photochem Photobiol 68:63-70, 1998; Fisher et al., N. Engl J Med 337:1419-1428, 1997; Kraemer, Proc Natl Acad Sci USA 94:11-14, 1997; Gilchrest, “Photodamage,” New York: Blackwell Scientific, 1995). Solar ultraviolet C (UVC) and much of ultraviolet B (UVB) are blocked by the ozone layer and oxygen in the earth's atmosphere. Approximately 95% of the ultraviolet radiation that reaches the earth's surface is ultraviolet A (UVA) while the remainder is UVB (Miller et al., Photochem Photobiol 68:63-70, 1998; Solar and ultraviolet radiation: World Health Organization, 1997), which plays a critical role in carcinogenesis by (1) forming DNA cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (Gilchrest et al., N Engl JMed 340:1341-8, 1999; Zhao et al., Int J Cancer 98:331-4, 2002), and (2) inducing immunosuppression (Noonan et al., Pigment Cell Res 16:16-25, 2003). Because of its longer wave length, UVA can pass through window glass and clothing, and penetrate deeper into the skin (Wang et al., J Am Acad Dermatol 44:837-846, 2001).
UVA radiation has been thought to be relatively innocuous because the amount of UVA absorbed by DNA is several orders of magnitude lower than that of UVB, but it has become evident that UVA damages DNA indirectly through generating oxidative free radicals and directly by inducing the formation of CPDs like UVB (Mouret et al., Proc Natl Acad Sci USA 103:13765-13770, 2006). Additionally, UVA has been suggested to play a role in melanoma development (Gasparro, Environ Health Perspect 108 Suppl 1:71-78, 2000; Setlow, J Investig Dermatol Symp Proc 4:46-49, 1999; Garland et al., Ann Epidemiol 3:103-110, 1993). Immune suppression may also be induced by UVA, further enhancing susceptibility to cutaneous malignancy (Nghiem et al., J Invest Dermatol 117:1193-1199, 2001; Bestak & Halliday, Photochem Photobiol 64:969-974, 1996).
Growing public awareness of the damaging effects of ultraviolet light/radiation in the 1960s led to the emergence of sun safety campaigns and the development of various sunscreens. The FDA now requires that all over-the-counter sunscreens undergo sun protection factor (SPF) testing. SPF is defined as a fold-increase of ultraviolet light exposure time needed to cause sunburn. For example, SPF 15 sunscreens extend the exposure time to induce erythema by 15-fold. Because UVB is 1,000 times more effective than UVA in producing erythema, SPF is a better measure of UVB blockade than UVA blockade. Currently, there are no standard in vivo assays to evaluate the UVA effects on human (or any other animal) skin, and it is difficult to assess a sunscreen for its real UVA protection efficacy despite the fact that many sunscreens on the market are advertised as blocking UVA in addition to UVB (Gasparro, Environ Health Perspect 108 Suppl 1:71-78, 2000; Lowe, Dermatol Clin 24:9-17, 2006; Rosenstein et al., Photodermatol Photoimmunol Photomed 15:75-80, 1999).
Although effects of ultraviolet light on the transcriptome of cultured keratinocytes have been reported (Becker et al., J Invest Dermatol 116:983-988, 2001; Dazard et al., Oncogene 22:2993-3006, 2003; Lee et al., Br J Dermatol 152:52-59, 2005; Li et al., FASEB J 15:2533-2535, 2001; Murakami et al., J Dermatol Sci 27:121-129, 2001; Pisarchik et al., Gene 341:199-207, 2004; Sesto et al., Proc Natl Acad Sci USA 99:2965-2970, 2002; Takao et al., Photodermatol Photoimmunol Photomed 18:5-13, 2002; Adachi et al., DNA Cell Biol 22:665-677, 2003), additional studies are needed to characterize how solar-simulated ultraviolet radiation (ssUVR) and UVA modify the global transcriptome of human skin in vivo (Enk et al., Photodermatol Photoimmunol Photomed 20:129-137, 2004; Blumenberg, OMICS 10:243-260, 2006).